The APC I1307K variant, more common in Ashkenazi Jewish (AJ) individuals, has been linked to a modest increase in colorectal cancer (CRC) risk. Analysis of over 460,000 UK Biobank participants found no statistically significant association between I1307K and CRC—or other cancers—in AJ or non-AJ white populations. However, the analysis was underpowered due to the variant’s rarity in non-AJ individuals and the limited number of cancer cases -particularly CRC- in AJ carriers. Much larger studies are needed to clarify risk. While ancestry can inform testing decisions, clinical management should be consistent across carriers, given the likely shared biological effect. [By Laura Valle (also on behalf of Clare Turnbull), https://jmg.bmj.com/content/early/2025/08/27/jmg-2025-110911 ]